Formation of adducts in the reaction of glyoxal with 2′-deoxyguanosine and with calf thymus DNA

The reactions of glyoxal with 2′-deoxyguanosine and calf thymus single- and double-stranded DNA in aqueous buffered solutions at physiological conditions resulted in the formation of two previously undetected adducts in addition to the known reaction product 3-(2′-deoxy-β-d-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx-dG). The adducts were isolated and purified by reversed-phase liquid chromatography and structurally characterised by UV absorbance, mass spectrometry, 1H and 13C NMR spectroscopy. The hitherto unknown adducts were identified as: 5-carboxymethyl-3-(2′-deoxy-β-d-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx2-dG) and N2-(carboxymethyl)-9-(2′-deoxy-β-d-erythro-pentofuranosyl)-purin-6(9H)-one (Gx1-dG). Both adducts were shown to arise from Gx-dG. Gx-dG and Gx2-dG were found to be unstable and partly transformed to Gx1-dG, which is a stable adduct and seems to be the end-product of the glyoxal reaction with 2′-deoxyguanosine. All adducts formed in the reaction of glyoxal with 2′-deoxyguanosine were observed in calf thymus DNA. Also in DNA, Gx1-dG was the only stable adduct. The transformation of Gx-dG to Gx1-dG seemed to take place in single-stranded DNA and therefore, Gx1-dG may be a potentially reliable biomarker for glyoxal exposure and may be involved in the genotoxic properties of the compound.

Graphical abstractThe glyoxal adducts formed in reactions with 2′-deoxyguanosine and with calf thymus DNA.Figure optionsDownload full-size imageDownload as PowerPoint slide